No More Running Blind In A Maze-The Laboratory Rat Genetic And Radiation Hybrid Map Is Here

April 30, 1999

A High-Density Integrated Genetic Linkage And Radiation Hybrid Map Of The Laboratory Rat

Considered a major, central, and essential resource for understanding genetics in the rat (Rattus norvegicus) -- one of the primary animal models for human medical research -- the completion of a high-density integrated genetic linkage and radiation hybrid map is a landmark in the field of genomic science. The rat map was a collaborative effort of several groups including researchers at the Medical College of Wisconsin, led by Howard Jacob, and The Whitehead Institute, led by Eric Lander.

The genetic linkage map presented in this report has a very dense coverage of genetic markers, with a total of 4,740 simple sequence-length polymorphisms (SSLPs) localized in relation to their position and relative distance from one another over the entire rat genome. This report also presents the first ever radiation hybrid map (RH Map) for the rat, which is a map that provides physical rather than genetic distance of genetic markers. The researchers then used common markers between the genetic and RH maps to integrate the two maps so that they can be used as a common and very valuable resource.

The rat has been used extensively for the past century as a model for comparative human behavioral and physical disorders, including alcoholism, autoimmunity disease, cancer, diabetes, neurobiological disorders, renal failure, toxicology, skeletal disease, hypertension, and more. These new maps will allow researchers previously hampered by an incomplete genetic infrastructure for the rat the means to connect disorders in the rat to their underlying genetic components and will give human geneticists an invaluable comparative tool for pinpointing related genes in humans that may be involved in human disease.
-end-
Contact Information:

Eric S. Lander
617-252-1906 (tel)
617-252-1902 (fax)
lander@genome.wi.mit.edu
Center for Genome Research
Whitehead Institute


Manuscript title and abstract are below; if desired, copies of map figures can be sent to you.

For complete manuscript or additional information, please contact:

Laurie Goodman, Ph.D.
Executive Editor
Genome Research
Phone 516-367-8325
FAX 516-367-8334
email: goodman@cshl.org
http://www.genome.orgA high-density integrated genetic linkage and radiation hybrid map of the laboratory rat

Robert Steen1*, Anne E. Kwitek-Black2*, Christopher Glenn3, Jo Gullings-Handley2, William Van Etten1, O. Scott Atkinson2, Diane Appel1, Simon Twigger2, Melanie Muir1, Tim Mull2, Mary Granados2, Mushira Kissebah2, Kerri Russo1, Robbin Crane1, Michael Popp3, Marc Peden3, Tara Matise4, Donna M. Brown5, Jian Lu2, Stephen Kingsmore3*, Peter J. Tonellato2, Steve Rozen1, Donna Slonim1, Peter Young1, Jonathan Rothberg3, Margit Knoblouch6, Abraham Provoost7, Detlev Ganten6, Steven D. Colman3, Jonathan Rothberg3, Eric S. Lander1, and Howard J. Jacob2

1. Center for Genome Research, Whitehead Institute for Biomedical Research and Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, Massachusetts, 02142 USA. 2. Medical College of Wisconsin, Department of Physiology, Laboratory for Genetic Research, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226 USA. 3. CuraGen Corp., 12085 Research Dr., Alachua, FL 32615 USA. 4. The Rockefeller University, New York, NY USA. 5. Research Genetics, 2130 Memorial Pkwy, Huntsville, AL 35801 USA. 6. Max Delbrück Center, Berlin-Büch, Germany. 7. Erasmus University, Department of Pediatric Surgery, Rotterdam, The Netherlands.

* Contributed equally

ABSTRACT

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4,740 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4,328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The radiation hybrid map is a framework map including 1,012 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to more than 3,000 genes and ESTs and more than 8,500 genetic markers (5,241 of our SSLPs and >3,500 SSLPs developed by other groups (Bihoreau, M.T., et al., 1997; M. James and A. Tanigami, RHdb (http://www.ebi.ac.uk/RHdb/index.html); R. Wilder, pers. comm. and http://www.nih.gov/niams/scientific/ratgbase). The RH map provides the means to rapidly localize genetic markers, genes and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.



Cold Spring Harbor Laboratory

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